The basis for the high expectations of cancer immunotherapy is in its ability to eliminate the residual malignant cells and prevent relapse of the disease. The simplest method is to induce tumor-specific immunity by immunizing patients with the antigenic components of their tumors, so called tumor-associated antigens (TAAs). However, TAAs are often poorly immunogenic and their repertoire for immunotherapeutic use is quite limited. Unlike solid tumors, immunotherapy for B cell malignancies is further hampered by lack of well defined TAAs, except for the patient's unique idiotypic antibody (Id). Although efficacy of the Id vaccines both in preclinical studies and phase I-II clinical tests is demonstrably potent2, a broader application of the vaccines may not be feasible due to the unpredictability of their T cell epitopes3, needed for T cell responses, and the suppressive nature of tumor derived Id in the absence of continuing T cell help4. In addition, Id vaccines have to be custom tailored and individually produced for each patient. Idiotypic vaccines for some B cell malignancies have been shown to be effective both in animal models9;32-34 and in phase I-III clinical trials35. However, a major limitation of this method is not only that the vaccine is individually produced for each patient (see review36;37), but also that the T cell epitopes essential for the protection may not always be expressed on Id.
Recently, the oncofetal Ag-immature laminin receptor 37-kDa protein, OFA-iLRP, was reported to be specifically expressed in different human tumors, such as breast, renal, lung and ovarian cancers, and in hematological malignancies1. OFA exists in two forms, as the dimerized high-affinity mature 67-kDa mLRP that may act as a cofactor to stabilize the binding of laminin to cell surface integrins, and the 37-kDa OFA-iLRP, which is not expressed by adult differentiated tissues5. The immunotherapeutic potential of OFA-iLRP has been recently proposed, as HLA-A2 specific CD8+ cells, generated from the peripheral blood of healthy donors or cancer patients, lysed OFA-iLRP+ acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) cells6;7.
Unlike Id, OFA-iLRP is highly evolutionary conserved antigen that contains number of CD8+ T cell epitopes expressed by human cancer cells7. Accordingly, a need exists for the development of anti-cancer vaccines that are not individually tailored and have broad ability to treat and prevent cancer, and OFA-iLRP may be useful if it can be made antigenic.